The unilateral ischemia produced in gerbils by the ipsilateral ligation of the common carotid artery is a satisfactory model for the investigation of both long-term ischemia and the recovery process following an ischemic insult. The changes in energy metabolites are essentially the same as those seen in short-term ischemia. Once these metabolites have reached a new steady state level, they remain constant for up to 6 hours of ischemia. During 6 hours of ischemia, the levels of dopamine, norepinephrine and 5-hydroxytryptamine decrease, while those of gamma aminobutyric acid increase. Cyclic AMP increases to a maximum at 2 hours and thereafter decreases to control levels by 6 hours. The recovery studies indicate that the metabolites of the ischemic cerebral cortex can be restored even after 1 or 3 hours of ischemia. However, certain events occur during the post-ischemic period which indicate that the responsiveness of the ischemic cerebral cortex to a second period of ischemia is severaly reduced. The initial ischemia apparently renders the cerebral cortex refractory to a secondary insult. The nature of the biochemical events involved in this process is currently being investigated.